Inhibition of Epstein-Barr virus reactivation by the flavonoid apigenin

Chung-Chun Wu,Sheng-Yen Huang,Jen-Yang Chen,Sheng-Ping Chou,Hui-Yu Hsu,Ching-Hwa Tsai,Chih-Yeu Fang,Yu-Jhen Cheng

doi:10.1186/s12929-016-0313-9

Abstract

BackgroundLytic reactivation of EBV has been reported to play an important role in human diseases, including NPC carcinogenesis. Inhibition of EBV reactivation is considered to be of great benefit in the treatment of virus-associated diseases. For this purpose, we screened for inhibitory compounds and found that apigenin, a flavonoid, seemed to have the ability to inhibit EBV reactivation.MethodsWe performed western blotting, immunofluorescence and luciferase analyses to determine whether apigenin has anti-EBV activity.ResultsApigenin inhibited expression of the EBV lytic proteins, Zta, Rta, EAD and DNase in epithelial and B cells. It also reduced the number of EBV-reactivating cells detectable by immunofluorescence analysis. In addition, apigenin has been found to reduce dramatically the production of EBV virions. Luciferase reporter analysis was performed to determine the mechanism by which apigenin inhibits EBV reactivation: apigenin suppressed the activity of the immediate-early (IE) gene Zta and Rta promoters, suggesting it can block initiation of the EBV lytic cycle.ConclusionTaken together, apigenin inhibits EBV reactivation by suppressing the promoter activities of two viral IE genes, suggesting apigenin is a potential dietary compound for prevention of EBV reactivation.

Highlights

Lytic reactivation of EBV has been reported to play an important role in human diseases, including nasopharyngeal carcinoma (NPC) carcinogenesis
In order to rule out the interference of toxic effects of apigenin treatment of the cells, we first tried to determine the cytotoxicity of apigenin to NPC cells
The results indicated that apigenin combined with TPA + sodium butyrate (SB) treatment did not cause severe cytotoxicity to the three cell lines (Additional file 1)

Summary

Introduction

Lytic reactivation of EBV has been reported to play an important role in human diseases, including NPC carcinogenesis. Epstein-Barr virus, a member of the γ-herpesviruses, infects most of the human population worldwide [1] It plays a causative role in infectious mononucleosis, hairy leukoplakia, and post-transplant lymphoproliferative disorder [1] and is highly associated with several human malignancies, including Burkitt’s lymphoma (BL) and nasopharyngeal carcinoma (NPC). EBV lytic proteins, such as viral DNase, terminase and kinase, have been shown to have the ability to induce genomic instability via different mechanisms [13,14,15]. These reports revealed that inhibition of EBV reactivation is

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Conclusion